In the synthesis of compounds with a carbon-carbon double bond, otherwise known as olefins or alkenes, typically, only one isomer (cis or trans) is desired. Syntheses are typically designed to produce only one isomer. However, a small amount of the undesired isomer is often produced. It is important to quantify the levels of all such undesired isomers as well as all other impurities in drug substance batches. One type of undesired isomer, in olefinic drug substances, is carbon-carbon double bond isomers. In order to quantify the levels of all drug substance-related impurities in drug substance batches, all impurities require analysis by an impurity assay.
Liquid chromatography is currently recognized as the most promising technology to achieve separation between carbon-carbon double bond isomers. Application of high pressure liquid chromatography (HPLC) techniques, in particular, for the separation of some isomers of carbon-carbon double bond compounds has in the past met with frustration, primarily due to the fact that it has been, heretofore, difficult to effect a satisfactory level of separation of cis and trans isomers that are structurally identical except for the geometric configuration of the carbon-carbon double bond. Although the prior art discloses various methods of separating cis and trans isomers using liquid or other chromatographic means, none has achieved a consistent and stable means for effecting separations in a reliable and reproducible manner for analytical and preparative uses.
Thus there still remains the continuing need to develop a liquid chromatography system to effectively separate cis and trans isomers of carbon-carbon double bond compounds.